BLOOD CLOTTING 113 



clotting factors of the blood has been demonstrated in this disease ; the 

 corpuscles and the platelets are normal in numbers, fibrinogen and cal- 

 cium salts are normal, and, as Howell has shown, there is no excess of 

 antithrombin. One significant fact, however, is that the addition of 

 thromboplastin or of its active ingredient, kephalin,. greatly shortens the 

 clotting time of the blood when it is removed by venipuncture. In agree- 

 ment with this observation it has been found that hemophilic blood clots 

 much more rapidly, indeed sometimes in the usual time, if it is allowed to 

 flow over cut or damaged tissue and so become mixed with thromboplas- 

 tin. These facts taken together would seem to indicate that the fault 

 must lie in a deficiency in prothrombin, and since this is derived mainly 

 from the platelets, which however are not decreased in number, we must 

 further assume that these elements have undergone some qualitative 

 change preventing their disintegration. An accompanying defect in 

 their agglutinating properties would at the same time explain their fail- 

 ure in hemophilia to clump together at the site of the hemorrhage so as 

 to block the smaller vessels with thrombi; hence the prolonged bleeding 

 time even after clotting has occurred. 



Thrombus Formation 



The first formed portion of a thrombus is paler than those formed later, 

 because it contains excessive numbers of platelets; and it seems clear 

 that it is by agglutination of these into masses, which then stick in the 

 blood vessels and by disintegrating shed forth prothrombin and thrombo- 

 plastin, that the clotting starts. This platelet agglutination may result 

 from stagnation in the bloodflow, or from roughening and damage to the 

 vessel walls. Stagnation may be due either to failure of the circulation 

 as a whole as in heart disease, or to local physical alterations in the vas- 

 cular tube, setting up conditions in which eddy currents with stagnant 

 pools of blood are formed, such as will occur at places where the vessels 

 suddenly become wider, as in varicose veins, in aneurisms and at the 

 sudden bend of large veins. The first formed (platelet) thrombus is fol- 

 lowed by one of a darker color, which fills the vessel up to the next 

 anastomotic branch. Similar stagnation may also follow the obstruc- 

 tion caused by lodgment of emboli in the smaller vessels (air, foreign 

 bodies in fine suspension, bacteria, etc.). The thrombi in such cases are 

 very small and occur particularly in the capillaries of the liver, spleen, 

 and lungs. The small thrombi often serve as foci from which clotting 

 spreads into the larger vessels, this being often encouraged by an increase 

 in the coagulability of the blood. When the intima is inflamed, it is pos- 

 sible that excessive amounts of thromboplastin are produced and that 

 this neutralizes the antithrombin in blood moving so slowly that it is not 



